Supervisor Project : Decoding the NEDD8 signal


Partner Lab


CNRS-CRBM scientists use modern technologies to address
fundamental questions in biochemistry and cell biology to better understand the
molecular bases of diseases and develop innovative therapeutic approaches.


Dimitris Xirodimas was educated in Athens, Greece, before moving to Scotland in 1991 for his undergraduate studies at the University of Dundee. After graduation with a 1st class Honours Biochemistry degree in 1995, he joined Prof. Sir David Lane’s laboratory as a PhD student and then as post-doctoral research assistant. His studies were focussed on the role of ubiquitin and ubiquitin-like molecules such as SUMO and NEDD8 in controlling the function of the p53 tumour suppressor. In 2004 he moved to the University of St-Andrews in Prof. Ronald Hay’s laboratory, as a post-doctoral research fellow and applied proteomic approaches for the identification of novel targets for the ubiquitin-like molecule NEDD8. In 2005, he established his own research team in the Wellcome Trust Centre for Gene Regulation and Expression at the University of Dundee through a Career Development Research Fellowship from the Association of International Cancer Research. In 2011 he established his laboratory at the CRBM-CNRS Institute in Montpellier and his research interest is on the role of ubiquitin and ubiquitin-like molecules in the cellular response to stress.

Summary of the Project

We have recently uncovered a diverse role of protein NEDDylation in the response to genotoxic and proteotoxic stress, which is independent of the established role for NEDD8 in CRL regulation. The NEDD8 response to the above-mentioned stimuli strictly depends on the formation of either poly-NEDD8 and mixed hybrid NEDD8-Ub chains respectively. Key objectives of the project are to dissect the molecular factors that control the formation of such signals and the mechanisms of recognition and processing either through the de-conjugation or proteolytic machineries (proteasome/autophagy pathways). Our goal is to determine the role of poly-NEDD8 and NEDD8-Ub hybrid chains as potential novel molecular signals for the cellular response to stress.